Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27–81), with performance status 0–2 were treated with merbarone 1000 mg/m 2 /day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-reponders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%–19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval of six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%), malaise (23%), weakness (20%), alopecia (17%), diarrhea (17%), anorexia (14%), transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5′nucleotidase increase (9%), and fever (9%). Hematologictoxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45186/1/10637_2004_Article_BF00872863.pd

Management zmen ve vzdelavani.

Available from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Selected pregnancy variables in women with placental abruption

Objective: The aim of this study was to investigate risk factors for placental abruption and to determine if anamnestic variables such as inherited thrombosis or recurrent fetal loss might be used as a predictor for placental abruption. Methods: A retrospective case-control study at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruptio out of 20,175 deliveries (0.79 %) who were compared to 196 unselected pregnant women. A detailed anamnesis was taken. Results: Compared to controls, women with placental abruptio had a 12-fold increased prevalence of prior recurrent fetal loss and a 6-fold increased prevalence of inherited thrombosis. Conclusions: We found that recurrent fetal loss, and inherited thrombosis may be significant risk factors for placental abruptio

Selected pregnancy variables in women with placental abruption

Objective: The aim of this study was to investigate risk factors for placental abruption and to determine if anamnestic variables such as inherited thrombosis or recurrent fetal loss might be used as a predictor for placental abruption. Methods: A retrospective case-control study at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruptio out of 20,175 deliveries (0.79 %) who were compared to 196 unselected pregnant women. A detailed anamnesis was taken. Results: Compared to controls, women with placental abruptio had a 12-fold increased prevalence of prior recurrent fetal loss and a 6-fold increased prevalence of inherited thrombosis. Conclusions: We found that recurrent fetal loss, and inherited thrombosis may be significant risk factors for placental abruptio

Frequency of selected thrombophilias in women with placental abruption

Objective: There is a growing view that inherited or acquired thrombophilia may predispose a woman towards an adverse pregnancy outcome. The aim of this study was to investigate whether risk factors for placental abruption because of such thrombophilias (such as carriership of factor V Leiden (FVL), prothrombin G20210A gene mutation and homozygous MTHFR C677T) might be used as a predictor for placental abruption. Methods: A retrospective case-control study conducted at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruption out of 20 175 deliveries (0.79%) were compared to 196 unselected gravidae. A detailed medical history was taken with special reference to factors related to hypercoagulation and blood was drawn for polymerase chain reaction analysis. The prevalence of FVL, prothrombin G20210A and MTHFR C677T was related to placental abruption. Results: The heterozygous form of FVL was present in 20of 142 cases (14.1%) in the placental abruption group, compared to ten of 196 (5.1%) in the control group (odds ratio 3.0, 95% confidence interval 1.4-6.7). Conclusions: We found that factor V Leiden is a significant risk factor for placental abruption

Evaluation of amonafide in disseminated malignant melanoma

Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA intercalating agent. This paper presents results of a phase II clinical study of AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine females, with biopsy proven malignant melanoma, performance status 0–2; median age 59 (range 29–74), and no previous chemotherapy, were treated with AMF 300 mg/m 2 /day by 60 min I.V. infusion for five days repeated every three weeks. Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement. None had known brain metastasis at entry. All 20 patients were evaluated for response and toxicity. Six patients had stable disease and fourteen had increasing disease. With 0/20 responses, the upper 95% confidence limit for the response rate was 14%. The median survival time was 5.7 months. Hematologic toxicity was dose limiting with the incidence of leucopenia 45% and thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We conclude that AMF administered at this dose and schedule is not active in the treatment of patients with malignant melanoma, previously untreated with chemotherapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45176/1/10637_2004_Article_BF00874160.pd